Over the recent years, immunomodulators have opened a new avenue in cancer treatment by virtue of their ability to boost the immune system for neoplastic cell elimination. Improving treatment outcomes by leveraging the interaction of these agents with traditional cancer treatments is the main emphasis of this review. Checkpoint inhibitors, chemokine receptors, and pattern recognition receptors are the immunological targets of their interactive mechanisms. Immunomodulators are generally categorized as inhibitors of checkpoint, cytokines, agonists, or adjuvants. Despite their high efficacy and specificity, modern-day antibody-based therapies face several key limitations such as immunogenicity, insufficient tissue penetration, and restricted oral bioavailability. To address these shortcomings, researchers are crafting small molecules with the potential for oral administration and improved pharmacokinetic properties. These agents can augment antibody therapies for synergistic effects to enhance therapeutic efficacy for different types of cancers. This review explores the synergy between immunomodulators and traditional cancer treatments (chemotherapy, radiation, and targeted therapies) as well as newer strategies like adoptive cell therapies (chimeric antigen receptor therapies such as chimeric antigen receptor-T (CAR-T) cell therapy and chimeric antigen receptor-natural killer (CAR-NK)). These combinations improve treatment effectiveness in a number of ways: radiotherapy increases tumor antigen presentation and T-cell infiltration, chemotherapy-induced immunogenic cell death boosts immune responses and targeted therapies lessen immunosuppression in the tumor microenvironment. Despite the potential appeal as adjuvants, immunomodulators also pose challenges in maximizing their efficacy and minimizing adverse effects. In this paper, clinical trials proving the effectiveness of these combined techniques are reviewed, and innovative approaches including next-generation checkpoint inhibitors and delivery systems based on nanoparticles are also highlighted. Overall, this review evaluates the existing impact of immunomodulatory adjuvants and their prospective trends in cancer care. Further development of immunomodulators will pave the way for more accessible and effective therapies, marking a significant step towards personalized oncological interventions.

The introduction of immunomodulators as adjuvant therapies in cancer treatment has represented a significant advancement in oncology, improving therapeutic response and patient survival. Emerging targets and molecules could provide new therapeutic opportunities for cancer patients. However, these agents can induce immunological side effects, including vasculitis and connective tissue diseases, which, while uncommon, present significant clinical challenges. This review analyzes the prevalence, clinical characteristics, therapeutic strategies, and management difficulties of vasculitis and connective tissue disorders triggered by immunomodulators in the context of cancer treatment. Although rare, these conditions significantly impact patients, demanding thorough management. Common rheumatological immune-related adverse events include inflammatory arthritis, Sjogren's disease, systemic lupus erythematosus, and systemic sclerosis, all of which require prompt recognition and appropriate intervention. Treatment frequently includes corticosteroids and immunosuppressive drugs, with new alternatives currently accessible. Efficient coordination between oncologists and rheumatologists enhances patient outcomes, highlighting the necessity for organized multidisciplinary strategies. Future research initiatives emphasize the identification of biomarkers for early diagnosis and the development of preventive methods to reduce immune-related adverse events in cancer therapy.